NAFLD as a Sexual Dimorphic Disease: Role of Gender and Reproductive Status in the Development and Progression of Nonalcoholic Fatty Liver Disease and Inherent Cardiovascular Risk.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical mechanisms and observational evidence without systematic methodology
PubMed 28526997 · doi:10.1007/s12325-017-0556-1
What was done
The authors synthesized evidence from animal models (overfed zebrafish, ovariectomized high-fat-fed mice) and human studies to evaluate the role of biological sex, reproductive stages, and estrogen exposure in the pathogenesis, progression, and cardiovascular risk of nonalcoholic fatty liver disease (NAFLD).
What was found
The abstract reports no numerical data or effect sizes. Female sex and young age are described as protective against dysmetabolism via preferential partitioning of fatty acids toward ketone bodies instead of very low density lipoprotein triacylglycerol, alongside adipose tissue browning. In animal models, ovarian senescence and estrogen deficiency accelerated steatosis, inflammation, and fibrosis. In humans, premenopausal women demonstrate lower rates of NAFLD and reduced risk of advanced fibrosis compared to men and postmenopausal women. However, early menarche is noted to associate with higher adult NAFLD risk primarily via excess adiposity, and postmenopausal estrogen loss is associated with severe steatosis and fibrosing nonalcoholic steatohepatitis.
Why it matters
This synthesis highlights biological sex and menopausal status as critical modifiers of NAFLD risk and fibrotic progression, informing risk stratification in clinical practice.
Limits
As a narrative review, it lacks a systematic literature search and quantitative meta-analysis. The abstract provides no quantitative human effect estimates, and mechanistic assertions rely partly on animal models with uncertain direct human equivalence.
Cited by
- supports Up to menopause women are protected against cardiometabolic conditions and fatty liver, but after menopause disease rates accelerate and catch up to men around age 60.